NM_016261.4:c.538-59C>A

Variant names:

• chr17-59878393-G-T
• rs12150500
• NM_016261.4:c.538-59C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016261.4(TUBD1):​c.538-59C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000927 in 1,079,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• Consequence: TUBD1 NM_016261.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132
• Publications: 0 publications found

Genes affected

TUBD1 (HGNC:16811): (tubulin delta 1) Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization; mitotic cell cycle; and positive regulation of smoothened signaling pathway. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016261.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBD1	NM_016261.4	MANE Select	c.538-59C>A		intron	N/A	NP_057345.2
	TUBD1	NM_001193609.2		c.538-59C>A		intron	N/A	NP_001180538.1
	TUBD1	NM_001193610.2		c.538-59C>A		intron	N/A	NP_001180539.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBD1	ENST00000325752.8	TSL:5 MANE Select	c.538-59C>A		intron	N/A	ENSP00000320797.3
	TUBD1	ENST00000592426.5	TSL:1	c.538-59C>A		intron	N/A	ENSP00000468518.1
	TUBD1	ENST00000340993.10	TSL:1	c.538-59C>A		intron	N/A	ENSP00000342399.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.27e-7 AC: 1 AN: 1079064 Hom.: 0 Cov.: 14 AF XY: 0.00000183 AC XY: 1 AN XY: 547198

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25344

American (AMR) AF: 0.00 AC: 0 AN: 40422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21884

East Asian (EAS) AF: 0.00 AC: 0 AN: 36726

South Asian (SAS) AF: 0.00 AC: 0 AN: 72896

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50750

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4948

European-Non Finnish (NFE) AF: 0.00000128 AC: 1 AN: 778710

Other (OTH) AF: 0.00 AC: 0 AN: 47384

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.92
DANN	Benign	0.75
PhyloP100		-0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12150500; hg19: chr17-57955754;